TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9104	27535;27536;27537	chr2:178712715;178712714;178712713	chr2:179577442;179577441;179577440
N2AB	8787	26584;26585;26586	chr2:178712715;178712714;178712713	chr2:179577442;179577441;179577440
N2A	7860	23803;23804;23805	chr2:178712715;178712714;178712713	chr2:179577442;179577441;179577440
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-76
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1153
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/I	rs2076843067	None	0.062	N	0.706	0.232	0.37568098594	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs2076843067	None	0.062	N	0.706	0.232	0.37568098594	gnomAD-4.0.0	3.04477E-06	None	None	None	None	N	None	3.49382E-05	0	None	0	0	None	0	0	1.20492E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.0659	likely_benign	0.0698	benign	-0.894	Destabilizing	None	N	0.174	neutral	N	0.414130644	None	None	N
T/C	0.4765	ambiguous	0.4897	ambiguous	-0.608	Destabilizing	0.824	D	0.737	prob.delet.	None	None	None	None	N
T/D	0.8832	likely_pathogenic	0.8896	pathogenic	-1.69	Destabilizing	0.38	N	0.776	deleterious	None	None	None	None	N
T/E	0.8189	likely_pathogenic	0.8425	pathogenic	-1.481	Destabilizing	0.149	N	0.749	deleterious	None	None	None	None	N
T/F	0.726	likely_pathogenic	0.7126	pathogenic	-0.399	Destabilizing	0.555	D	0.778	deleterious	None	None	None	None	N
T/G	0.3707	ambiguous	0.3543	ambiguous	-1.338	Destabilizing	0.081	N	0.669	neutral	None	None	None	None	N
T/H	0.7588	likely_pathogenic	0.7679	pathogenic	-1.61	Destabilizing	0.935	D	0.723	prob.delet.	None	None	None	None	N
T/I	0.3954	ambiguous	0.3975	ambiguous	0.279	Stabilizing	0.062	N	0.706	prob.neutral	N	0.504080644	None	None	N
T/K	0.7687	likely_pathogenic	0.792	pathogenic	-0.681	Destabilizing	0.117	N	0.75	deleterious	N	0.509179089	None	None	N
T/L	0.2912	likely_benign	0.2851	benign	0.279	Stabilizing	0.035	N	0.645	neutral	None	None	None	None	N
T/M	0.1997	likely_benign	0.2	benign	0.309	Stabilizing	0.555	D	0.747	deleterious	None	None	None	None	N
T/N	0.48	ambiguous	0.4827	ambiguous	-1.437	Destabilizing	0.555	D	0.711	prob.delet.	None	None	None	None	N
T/P	0.7716	likely_pathogenic	0.7629	pathogenic	-0.08	Destabilizing	0.317	N	0.782	deleterious	N	0.509432579	None	None	N
T/Q	0.6756	likely_pathogenic	0.697	pathogenic	-1.097	Destabilizing	0.555	D	0.782	deleterious	None	None	None	None	N
T/R	0.6463	likely_pathogenic	0.6756	pathogenic	-1.029	Destabilizing	0.317	N	0.779	deleterious	N	0.520535395	None	None	N
T/S	0.1572	likely_benign	0.1495	benign	-1.555	Destabilizing	0.027	N	0.549	neutral	N	0.481033213	None	None	N
T/V	0.2	likely_benign	0.2027	benign	-0.08	Destabilizing	0.002	N	0.244	neutral	None	None	None	None	N
T/W	0.9513	likely_pathogenic	0.9466	pathogenic	-0.726	Destabilizing	0.935	D	0.739	prob.delet.	None	None	None	None	N
T/Y	0.8139	likely_pathogenic	0.8193	pathogenic	-0.323	Destabilizing	0.555	D	0.767	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.